1) Following a brief exposure of cultured cells to 125-I-choleragen, adenylate cyclase remained persistently activated. The affinity of 125-I-toxin for intact cells obtained by kinetic analysis was similar to that of free toxin for GM1-oligosaccharide. Total 125-I-choleragen incorporated into cells was degraded with a half-life of greater than 24 hr. The slow degradation of the toxin may explain the continued activation of cyclase following a brief exposure of cells to toxin. 2) Interaction of Escherichia coli heat-labile enterotoxin (LT) with GM1 and its oligosaccharide was similar to that observed with choleragen; both toxins may share similar ganglioside receptors. In contrast to choleragen, the ADP-ribosyltransferase activity of LT was not fully expressed without prior trypsinization to activate the catalytic subunit. 3) A histone-dependent NAD glycohydrolase was identified in rat liver; histone was required for hydrolysis of NAD and for the pyridine base exchange reaction. A histone-dependent NAD: arginine ADP-ribosyltransferase was converted from an active high molecular weight species to an active protomeric form by histone; a similar transition was not observed with the glycohydrolase. Activation of the ADP-ribosyltransferase and the NAD glycohydrolase by histone was rapid and reversible.